Adipose stem cells ameliorate erectile dysfunction in diabetes mellitus rats by attenuating ferroptosis through NRP1 with SLC7A11 interaction

IF 7.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Free Radical Biology and Medicine Pub Date : 2025-02-26 DOI:10.1016/j.freeradbiomed.2025.02.041

Jun-qi Luo , Li Wang , Zi-qi Liao , Bing-xin Lu , Cai-yu Luo , Hai-yang He , Zhi-han Ou yang , Song-bo Duan , Shu-hua He , An-yang Wei , Hai-bo Zhang

{"title":"Adipose stem cells ameliorate erectile dysfunction in diabetes mellitus rats by attenuating ferroptosis through NRP1 with SLC7A11 interaction","authors":"Jun-qi Luo , Li Wang , Zi-qi Liao , Bing-xin Lu , Cai-yu Luo , Hai-yang He , Zhi-han Ou yang , Song-bo Duan , Shu-hua He , An-yang Wei , Hai-bo Zhang","doi":"10.1016/j.freeradbiomed.2025.02.041","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Adipose stem cells (ADSCs) have garneVred increasing attention for their potential to treat diabetes mellitus erectile dysfunction (DMED), but the underlying molecular mechanisms remain unclear. The aim of this study was to identify and investigate the key cytokines and mechanisms by which ADSCs improve erectile function in DMED rats.</div></div><div><h3>Methods</h3><div>We performed in vivo and in vitro assays, including rat erectile function assessment, cell co-culture, cytokine microarray screening and co-immunoprecipitation to investigate the role of ADSCs in improving erectile function in DMED rats.</div></div><div><h3>Results</h3><div>Our analyses confirmed the occurrence of ferroptosis in the corpus cavernosum of DMED rats, while ADSCs treatment significantly restored erectile function and improved relevant indicators of ferroptosis. In vitro assays further indicated that corpus cavernosum smooth muscle cells (CCSMCs) co-cultured with ADSCs exhibited enhanced resistance to ferroptosis, with notably lower levels of cytoplasmic and lipid reactive oxygen species compared to the ferroptosis inducer Erastin-treated group. Mechanistic studies revealed that Neuropilin 1 (NRP1) may be a key molecule in ADSCs to improve erectile function in DMED rats. Furthermore, NRP1 in CCSMCs can interact with solute carrier family 7 member 11 (SLC7A11) to enhance the function of the glutamate-cysteine countertransport (Xc-) system and ferroptosis resistance in CCSMCs.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings indicate that NRP1 is a key molecule for ADSCs treatment to alleviate ferroptosis and improve erectile function in DMED rats, providing a promising target for DMED treatment and prognosis.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"232 ","pages":"Pages 40-55"},"PeriodicalIF":7.1000,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Free Radical Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891584925001248","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Adipose stem cells (ADSCs) have garneVred increasing attention for their potential to treat diabetes mellitus erectile dysfunction (DMED), but the underlying molecular mechanisms remain unclear. The aim of this study was to identify and investigate the key cytokines and mechanisms by which ADSCs improve erectile function in DMED rats.

Methods

We performed in vivo and in vitro assays, including rat erectile function assessment, cell co-culture, cytokine microarray screening and co-immunoprecipitation to investigate the role of ADSCs in improving erectile function in DMED rats.

Results

Our analyses confirmed the occurrence of ferroptosis in the corpus cavernosum of DMED rats, while ADSCs treatment significantly restored erectile function and improved relevant indicators of ferroptosis. In vitro assays further indicated that corpus cavernosum smooth muscle cells (CCSMCs) co-cultured with ADSCs exhibited enhanced resistance to ferroptosis, with notably lower levels of cytoplasmic and lipid reactive oxygen species compared to the ferroptosis inducer Erastin-treated group. Mechanistic studies revealed that Neuropilin 1 (NRP1) may be a key molecule in ADSCs to improve erectile function in DMED rats. Furthermore, NRP1 in CCSMCs can interact with solute carrier family 7 member 11 (SLC7A11) to enhance the function of the glutamate-cysteine countertransport (Xc-) system and ferroptosis resistance in CCSMCs.

Conclusion

In conclusion, our findings indicate that NRP1 is a key molecule for ADSCs treatment to alleviate ferroptosis and improve erectile function in DMED rats, providing a promising target for DMED treatment and prognosis.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Free Radical Biology and Medicine 医学-内分泌学与代谢

CiteScore

14.00

自引率

4.10%

发文量

850

审稿时长

22 days

期刊介绍： Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.